It is known that certain mevalonate derivatives inhibit the biosynthesis of cholesterol, cf F. M. Singer, et al., Proc. Soc. Exper. Biol. Med., 102, 270 (1959) and F. H. Hulcher, Arch. Biochem. Biophys., 146, 422 (1971), Nevertheless, the activity of these known compounds has not always been found to be satisfactory, i.e. to have practical application.
Recently, Endo et al, reported (U.S. Pat. No. 4,049,495, U.S. Pat. No. 4,137,322 and U.S. Pat. No. 3,983,140) the production of a fermentation product which was quite active in the inhibition of cholesterol biosynthesis. This natural product, now called compactin, was reported by Brown et al., (J. Chem. Soc. Perkin I, 1165 (1976)) to have a complex mevalonolactone structure.
A recent Belgian Pat. No. 867,421 disclosed a group of synthetic compounds of the generic formula II ##STR3## in which E represents a direct bond, a C.sub.1-3 alkylene bridge or a vinylene bridge and the various R's represent a variety of substitutents.
The activity reported in the Belgian patent is less than 1% that of compactin.